Alkylnitrosoureas, because of their clinical simplicity and known catabolism as well as their ability to induce a high incidence of neurogenic tumors, provide an excellent opportunity to study the basic problem of neoplastic transformation. It is the objective of this proposal to examine the involvement of selected forms of DNA damage induced by nitrosourea compounds during the initiation stage of neoplastic transformation and to detect and characterize changes in selected cellular functions occurring as a consequence of such DNA damages and determine the importance of these changes for neoplastic transformation. Specifically, we will first determine the molecular biochemical interactions of nitrosoureas with the genetic material and the effects of these interactions on transcription. We will further explore the effects of these compounds on chromosal events at different phases of the cell cycle. We will also test the role of nerve growth factor in suppression or regression of neoplastic transformation.